Stomatal conductance (gs) determines CO2 uptake for photosynthesis (A) and water loss through transpiration, which is essential for evaporative cooling and maintenance of optimal leaf temperature as well as nutrient uptake. Stomata adjust their aperture to maintain an appropriate balance between CO2 uptake and water loss and are therefore critical to overall plant water status and productivity. Although there is considerable knowledge regarding guard cell (GC) osmoregulation (which drives differences in GC volume and therefore stomatal opening and closing), as well as the various signal transduction pathways that enable GCs to sense and respond to different environmental stimuli, little is known about the signals that coordinate mesophyll demands for CO2. Furthermore, chloroplasts are a key feature in GCs of many species, however, their role in stomatal function is unclear and a subject of debate. In this review we explore the current evidence regarding the role of these organelles in stomatal behaviour, including GC electron transport and Calvin-Benson-Bassham (CBB) cycle activity as well as their possible involvement correlating gs and A along with other potential mesophyll signals. We also examine the roles of other GC metabolic processes in stomatal function.

Transcriptional and post-transcriptional regulations control gene expression in most cells. However, critical transitions during the development of the female gamete relies exclusively on regulation of mRNA translation in the absence of de novo mRNA synthesis. Specific temporal patterns of maternal mRNA translation are essential for the oocyte progression through meiosis, for generation of a haploid gamete ready for fertilization and for embryo development. In this review, we will discuss how mRNAs are translated during oocyte growth and maturation using mostly a genome-wide perspective. This broad view on how translation is regulated reveals multiple divergent translational control mechanisms required to coordinate protein synthesis with progression through the meiotic cell cycle and with development of a totipotent zygote.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) are two enzymes of the Calvin Benson cycle that stand out for some peculiar properties they have in common: (i) they both use the products of light reactions for catalysis (NADPH for GAPDH, ATP for PRK), (ii) they are both light-regulated through thioredoxins and (iii) they are both involved in the formation of regulatory supramolecular complexes in the dark or low photosynthetic conditions, with or without the regulatory protein CP12. In the complexes, enzymes are transiently inactivated but ready to recover full activity after complex dissociation. Fully active GAPDH and PRK are in large excess for the functioning of the Calvin-Benson cycle, but they can limit the cycle upon complex formation. Complex dissociation contributes to photosynthetic induction. CP12 also controls PRK concentration in model photosynthetic organisms like Arabidopsis thaliana and Chlamydomonas reinhardtii. The review combines in vivo and in vitro data into an integrated physiological view of the role of GAPDH and PRK dark complexes in the regulation of photosynthesis.

Adult females and males of most species differ in many aspects of their morphology, physiology and behavior, in response to sex-specific selective pressures that maximize fitness. While we have an increasingly good understanding of the genetic mechanisms that initiate these differences, the sex-specific developmental trajectories that generate them are much less well understood. Here we review recent advances in the sex-specific regulation of development focusing on two models where this development is increasingly well understood: Sexual dimorphism of body size in the fruit fly Drosophila melanogaster and sexual dimorphism of horns in the horned beetle Onthophagus taurus. Because growth and development are also supported by metabolism, the regulation of sex-specific metabolism during and after development is an important aspect of the generation of female and male phenotypes. Hitherto, the study of sex-specific development has largely been independent of the study of sex-specific metabolism. Nevertheless, as we discuss in this review, recent research has begun to reveal considerable overlap in the cellular and physiological mechanisms that regulate sex-specific development and metabolism.

The neural crest is a vertebrate-specific embryonic stem cell population that gives rise to a vast array of cell types throughout the animal body plan. These cells are first born at the edges of the central nervous system, from which they migrate extensively and differentiate into multiple cellular derivatives. Given the unique set of structures these cells comprise, the origin of the neural crest is thought to have important implications for the evolution and diversification of the vertebrate clade. In jawed vertebrates, neural crest cells exist as distinct subpopulations along the anterior-posterior axis. These subpopulations differ in terms of their respective differentiation potential and cellular derivatives. Thus, the modern neural crest is characterized as multipotent, migratory, and regionally segregated throughout the embryo. Here, we retrace the evolutionary origins of the neural crest, from the appearance of conserved regulatory circuitry in basal chordates to the emergence of neural crest subpopulations in higher vertebrates. Finally, we discuss a stepwise trajectory by which these cells may have arisen and diversified throughout vertebrate evolution.

Since the discovery of this cell population by His in 1850, the neural crest has been under intense study for its important role during vertebrate development. Much has been learned about the function and regulation of neural crest cell differentiation, and as a result, the neural crest has become a key model system for stem cell biology in general. The experiments performed in embryology, genetics, and cell biology in the last 150 years in the neural crest field has given rise to several big questions that have been debated intensely for many years: "How does positional information impact developmental potential? Are neural crest cells individually multipotent or a mixed population of committed progenitors? What are the key factors that regulate the acquisition of stem cell identity, and how does a stem cell decide to differentiate towards one cell fate versus another?" Recently, a marriage between single cell multi-omics, statistical modeling, and developmental biology has shed a substantial amount of light on these questions, and has paved a clear path for future researchers in the field.

The neural crest (NC) is an emblematic population of embryonic stem-like cells with remarkable migratory ability. These distinctive attributes have inspired the curiosity of developmental biologists for over 150 years, however only recently the regulatory mechanisms controlling the complex features of the NC have started to become elucidated at genomic scales. Regulatory control of NC development is achieved through combinatorial transcription factor binding and recruitment of associated transcriptional complexes to distal cis-regulatory elements. Together, they regulate when, where and to what extent transcriptional programmes are actively deployed, ultimately shaping ontogenetic processes. Here, we discuss how transcriptional networks control NC ontogeny, with a special emphasis on the molecular mechanisms underlying specification of the cephalic NC. We also cover emerging properties of transcriptional regulation revealed in diverse developmental systems, such as the role of three-dimensional conformation of chromatin, and how they are involved in the regulation of NC ontogeny. Finally, we highlight how advances in deciphering the NC transcriptional network have afforded new insights into the molecular basis of human diseases.

Of all the cell types arising from the neural crest, ectomesenchyme is likely the most unusual. In contrast to the neuroglial cells generated by neural crest throughout the embryo, consistent with its ectodermal origin, cranial neural crest-derived cells (CNCCs) generate many connective tissue and skeletal cell types in common with mesoderm. Whether this ectoderm-derived mesenchyme (ectomesenchyme) potential reflects a distinct developmental origin from other CNCC lineages, and/or epigenetic reprogramming of the ectoderm, remains debated. Whereas decades of lineage tracing studies have defined the potential of CNCC ectomesenchyme, these are being revisited by modern genetic techniques. Recent work is also shedding light on the extent to which intrinsic and extrinsic cues determine ectomesenchyme potential, and whether maintenance or reacquisition of CNCC multipotency influences craniofacial repair.

Infection with pathogenic microbes is a severe threat that hosts manage by activating the innate immune response. In Drosophila melanogaster, the Toll and Imd signaling pathways are activated by pathogen-associated molecular patterns to initiate cellular and humoral immune processes that neutralize and kill invaders. The Toll and Imd signaling pathways operate in organs such as fat body and gut that control host nutrient metabolism, and infections or genetic activation of Toll and Imd signaling also induce wide-ranging changes in host lipid, carbohydrate and protein metabolism. Metabolic regulation by immune signaling can confer resistance to or tolerance of infection, but it can also lead to pathology and susceptibility to infection. These immunometabolic phenotypes are described in this review, as are changes in endocrine signaling and gene regulation that mediate survival during infection. Future work in the field is anticipated to determine key variables such as sex, dietary nutrients, life stage, and pathogen characteristics that modify immunometabolic phenotypes and, importantly, to uncover the mechanisms used by the immune system to regulate metabolism.

Developing embryos are metabolically active, open systems that constantly exchange matter and energy with their environment. They function out of thermodynamic equilibrium and continuously use metabolic pathways to obtain energy from maternal nutrients, in order to fulfill the energetic requirements of growth and development. While an increasing number of studies highlight the role of metabolism in different developmental contexts, the physicochemical basis of embryogenesis, or how cellular processes use energy and matter to act together and transform a zygote into an adult organism, remains unknown. As we obtain a better understanding of metabolism, and benefit from current technology development, it is a promising time to revisit the energetic cost of development and how energetic principles may govern embryogenesis. Here, we review recent advances in methodology to measure and infer energetic parameters in developing embryos. We highlight a potential common pattern in embryonic energy expenditure and metabolic strategy across animal embryogenesis, and discuss challenges and open questions in developmental energetics.

During development of the vertebrate sensory system, many important components like the sense organs and cranial sensory ganglia arise within the head and neck. Two progenitor populations, the neural crest, and cranial ectodermal placodes, contribute to these developing vertebrate peripheral sensory structures. The interactions and contributions of these cell populations to the development of the lens, olfactory, otic, pituitary gland, and cranial ganglia are vital for appropriate peripheral nervous system development. Here, we review the origins of both neural crest and placode cells at the neural plate border of the early vertebrate embryo and investigate the molecular and environmental signals that influence specification of different sensory regions. Finally, we discuss the underlying molecular pathways contributing to the complex vertebrate sensory system from an evolutionary perspective, from basal vertebrates to amniotes.

Epithelial to mesenchymal transition (EMT) is a well-defined cellular process that was discovered in chicken embryos and described as "epithelial to mesenchymal transformation" [1]. During EMT, epithelial cells lose their epithelial features and acquire mesenchymal character with migratory potential. EMT has subsequently been shown to be essential for both developmental and pathological processes including embryo morphogenesis, wound healing, tissue fibrosis and cancer [2]. During the past 5 years, interest and study of EMT especially in cancer biology have increased exponentially due to the implied role of EMT in multiple aspects of malignancy such as cell invasion, survival, stemness, metastasis, therapeutic resistance and tumor heterogeneity [3]. Since the process of EMT in embryogenesis and cancer progression shares similar phenotypic changes, core transcription factors and molecular mechanisms, it has been proposed that the initiation and development of carcinoma could be attributed to abnormal activation of EMT factors usually required for normal embryo development. Therefore, developmental EMT mechanisms, whose timing, location, and tissue origin are strictly regulated, could prove useful for uncovering new insights into the phenotypic changes and corresponding gene regulatory control of EMT under pathological conditions. In this review, we initially provide an overview of the phenotypic and molecular mechanisms involved in EMT and discuss the newly emerging concept of epithelial to mesenchymal plasticity (EMP). Then we focus on our current knowledge of a classic developmental EMT event, neural crest cell (NCC) delamination, highlighting key differences in our understanding of NCC EMT between mammalian and non-mammalian species. Lastly, we highlight available tools and future directions to advance our understanding of mammalian NCC EMT.

Over the last decade, the combination of genetics, transcriptomic and proteomic approaches yielded substantial insights into the mechanisms behind the synthesis and breakdown of energy stores in the model organisms. The fruit fly Drosophila melanogaster has been particularly useful to unravel genetic regulations of energy metabolism. Despite the considerable evolutionary distance between humans and flies, the energy storage organs, main metabolic pathways, and even their genetic regulations remained relatively conserved. Glycogen and fat are universal energy reserves used in all animal phyla and several of their endocrine regulators, such as the insulin pathway, are highly evolutionarily conserved. Nevertheless, some of the factors inducing catabolism of energy stores have diverged significantly during evolution. Moreover, even within a single insect species, D. melanogaster, there are substantial developmental and context-dependent variances in the regulation of energy stores. These differences include, among others, the endocrine pathways that govern the catabolic events or the predominant fuel which is utilized for the given process. For example, many catabolic regulators that control energy reserves in adulthood seem to be largely dispensable for energy mobilization during development. In this review, we focus on a selection of the most important catabolic regulators from the group of peptide hormones (Adipokinetic hormone, Corazonin), catecholamines (octopamine), steroid hormones (20-hydroxyecdysone), and other factors (extracellular adenosine, regulators of lipase Brummer). We discuss their roles in the mobilization of energy reserves for processes such as development through non-feeding stages, flight or starvation survival. Finally, we conclude with future perspectives on the energy balance research in the fly model.

Mitochondria are vital organelles with a central role in all aspects of cellular metabolism. As a means to support the ever-changing demands of the cell, mitochondria produce energy, drive biosynthetic processes, maintain redox homeostasis, and function as a hub for cell signaling. While mitochondria have been widely studied for their role in disease and metabolic dysfunction, this organelle has a continually evolving role in the regulation of development, wound repair, and regeneration. Mitochondrial metabolism dynamically changes as tissues transition through distinct phases of development. These organelles support the energetic and biosynthetic demands of developing cells and function as key structures that coordinate the nutrient status of the organism with developmental progression. This review will examine the mechanisms that link mitochondria to developmental processes. We will also examine the process of mitochondrial respiratory quiescence (MRQ), a novel mechanism for regulating cellular metabolism through the biochemical and physiological remodeling of mitochondria. Lastly, we will examine MRQ as a system to discover the mechanisms that drive mitochondrial remodeling during development.

Neural crest cells are central to vertebrate development and evolution, endowing vertebrates with a "new head" that resulted in morphological, physiological, and behavioral features that allowed vertebrates to become active predators. One remarkable feature of neural crest cells is their multi-germ layer potential that allows for the formation of both ectodermal (pigmentation, peripheral glia, sensory neurons) and mesenchymal (connective tissue, cartilage/bone, dermis) cell types. Understanding the cellular and evolutionary origins of this broad cellular potential in the neural crest has been a long-standing focus for developmental biologists. Here, we review recent work that has demonstrated that neural crest cells share key features with pluripotent blastula stem cells, including expression of the Yamanaka stem cell factors (Oct3/4, Klf4, Sox2, c-Myc). These shared features suggest that pluripotency is either retained in the neural crest from blastula stages or subsequently reactivated as the neural crest forms. We highlight the cellular and molecular parallels between blastula stem cells and neural crest cells and discuss the work that has led to current models for the cellular origins of broad potential in the crest. Finally, we explore how these themes can provide new insights into how and when neural crest cells and pluripotency evolved in vertebrates and the evolutionary relationship between these populations.

Accumulating evidence has illustrated that the E3 ubiquitin ligases critically participate in the development and progression of cardiovascular diseases. Dysregulation of E3 ubiquitin ligases exacerbates cardiovascular diseases. Blockade or activation of E3 ubiquitin ligases mitigates cardiovascular performance. Therefore, in this review, we mainly introduced the critical role and underlying molecular mechanisms of E3 ubiquitin ligase NEDD4 family in governing the initiation and progression of cardiovascular diseases, including ITCH, WWP1, WWP2, Smurf1, Smurf2, Nedd4-1 and Nedd4-2. Moreover, the functions and molecular insights of other E3 ubiquitin ligases, such as F-box proteins, in cardiovascular disease development and malignant progression are described. Furthermore, we illustrate several compounds that alter the expression of E3 ubiquitin ligases to alleviate cardiovascular diseases. Therefore, modulation of E3 ubiquitin ligases could be a novel and promising strategy for improvement of therapeutic efficacy of deteriorative cardiovascular diseases.

The Calvin Benson cycle in phototrophic and chemolithoautotrophic bacteria has ecological and biotechnological importance, which has motivated study of its regulation. I review recent advances in our understanding of how the Calvin Benson cycle is regulated in bacteria and the technologies used to elucidate regulation and modify it, and highlight differences between and photoautotrophic and chemolithoautotrophic models. Systems biology studies have shown that in oxygenic phototrophic bacteria, Calvin Benson cycle enzymes are extensively regulated at post-transcriptional and post-translational levels, with multiple enzyme activities connected to cellular redox status through thioredoxin. In chemolithoautotrophic bacteria, regulation is primarily at the transcriptional level, with effector metabolites transducing cell status, though new methods should now allow facile, proteome-wide exploration of biochemical regulation in these models. A biotechnological objective is to enhance CO2 fixation in the cycle and partition that carbon to a product of interest. Flux control of CO2 fixation is distributed over multiple enzymes, and attempts to modulate gene Calvin cycle gene expression show a robust homeostatic regulation of growth rate, though the synthesis rates of products can be significantly increased. Therefore, de-regulation of cycle enzymes through protein engineering may be necessary to increase fluxes. Non-canonical Calvin Benson cycles, if implemented with synthetic biology, could have reduced energy demand and enzyme loading, thus increasing the attractiveness of these bacteria for industrial applications.

Sporotrichosis, a fungal disease, is caused by exposure to soil that harbors Sporothrix schenckii or through inhalation of fungal spores. Skin is the most frequently exposed organ making sporotrichosis a primarily dermal disease. Many described reports in the literature suggest a connection of sporotrichosis with cutaneous squamous cell carcinoma with some connection between initial sporotrichosis diagnosis and treatment followed by development of cutaneous squamous cell carcinoma at the very site. Conversely, there is also evidence for sporotrichosis subsequent to skin cancer diagnosis, even after cancer chemotherapy, which points towards weakening of immune response by cancer chemotherapy leading to attack and infection by Sporothrix schenckii. We also propose and focus on inflammation as the connection between sporotrichosis, cancer and even the metastatic spread of cancer. Inflammation-associated IL-6, IFN-γ, natural killer cells and M2-macrophages possibly mechanistically link sporotrichosis with cancer, particularly cutaneous squamous cell carcinoma. These inflammation related factors/cells are regulated epigenetically raising the possibility of epigenetic regulation of sporotrichosis, which has not been described yet in the available literature. Clinical management of inflammation may thus be effective strategy not just against sporotrichosis but also the related onset of cutaneous squamous cell carcinoma and possibly its metastasis to lymph nodes.

The nematode Caenorhabditis elegans has been a model for studying infection since the early 2000s and many major discoveries have been made regarding its innate immune responses. C. elegans has been found to utilize some key conserved aspects of immune responses and signaling, but new interesting features of innate immunity have also been discovered in the organism that might have broader implications in higher eukaryotes such as mammals. Some of the distinctive features of C. elegans innate immunity involve the mechanisms this bacterivore uses to detect infection and mount specific immune responses to different pathogens, despite lacking putative orthologs of many important innate immune components, including cellular immunity, the inflammasome, complement, or melanization. Even when orthologs of known immune factors exist, there appears to be an absence of canonical functions, most notably the lack of pattern recognition by its sole Toll-like receptor. Instead, recent research suggests that C. elegans senses infection by specific pathogens through contextual information, including unique products produced by the pathogen or infection-induced disruption of host physiology, similar to the proposed detection of patterns of pathogenesis in mammalian systems. Interestingly, C. elegans can also transfer information of past infection to their progeny, providing robust protection for their offspring in face of persisting pathogens, in part through the RNAi pathway as well as potential new mechanisms that remain to be elucidated. Altogether, some of these strategies employed by C. elegans share key conceptual features with vertebrate adaptive immunity, as the animal can differentiate specific microbial features, as well as propagate a form of immune memory to their offspring.

Cells entrust ribosomes with the critical task of identifying problematic mRNAs and facilitating their degradation. Ribosomes must communicate when they encounter and stall on an aberrant mRNA, lest they expose the cell to toxic and disease-causing proteins, or they jeopardize ribosome homeostasis and cellular translation. In recent years, ribosomal ubiquitination has emerged as a central signaling step in this process, and proteomic studies across labs and experimental systems show a myriad of ubiquitination sites throughout the ribosome. Work from many labs zeroed in on ubiquitination in one region of the small ribosomal subunit as being functionally significant, with the balance and exact ubiquitination sites determined by stall type, E3 ubiquitin ligases, and deubiquitinases. This review discusses the current literature surrounding ribosomal ubiquitination during translational stress and considers its role in committing translational complexes to decay.

Translation is regulated spatiotemporally to direct protein synthesis when and where it is needed. RNA localization and local translation have been observed in various subcellular compartments, allowing cells to rapidly and finely adjust their proteome post-transcriptionally. Local translation on membrane-bound organelles is important to efficiently synthesize proteins targeted to the organelles. Protein-RNA phase condensates restrict RNA spatially in membraneless organelles and play essential roles in translation regulation and RNA metabolism. In addition, the temporal translation kinetics not only determine the amount of protein produced, but also serve as an important checkpoint for the quality of ribosomes, mRNAs, and nascent proteins. Translation imaging provides a unique capability to study these fundamental processes in the native environment. Recent breakthroughs in imaging enabled real-time visualization of translation of single mRNAs, making it possible to determine the spatial distribution and key biochemical parameters of in vivo translation dynamics. Here we reviewed the recent advances in translation imaging methods and their applications to study spatiotemporal translation regulation in vivo.

The Calvin-Benson cycle (CBC) evolved over 2 billion years ago but has been subject to massive selection due to falling atmospheric carbon dioxide, rising atmospheric oxygen and changing nutrient and water availability. In addition, large groups of organisms have evolved carbon-concentrating mechanisms (CCMs) that operate upstream of the CBC. Most previous studies of CBC diversity focused on Rubisco kinetics and regulation. Quantitative metabolite profiling provides a top-down strategy to uncover inter-species diversity in CBC operation. CBC profiles were recently published for twenty species including terrestrial C3 species, terrestrial C4 species that operate a biochemical CCM, and cyanobacteria and green algae that operate different types of biophysical CCM. Distinctive profiles were found for species with different modes of photosynthesis, revealing that evolution of the various CCMs was accompanied by co-evolution of the CBC. Diversity was also found between species that share the same mode of photosynthesis, reflecting lineage-dependent diversity of the CBC. Connectivity analysis uncovers constraints due to pathway and thermodynamic topology, and reveals that cross-species diversity in the CBC is driven by changes in the balance between regulated enzymes and in the balance between the CBC and the light reactions or end-product synthesis.

Polycystic ovary syndrome (PCOS) refers to a condition that often has 'poly' liquid containing sacks around ovaries. It affects reproductive-aged females giving rise to menstrual and related reproductive issues. PCOS is marked by hormonal imbalance often resulting in hyperandrogenism. Inflammation is now considered a central manifestation of this disease with several inflammatory biomarkers such as TNF-α, C-reactive protein and Interleukins-6/18 found to be particularly elevated in PCOS patients. Diagnosis is often late, and MRI-based diagnosis, along with blood-based analyses, are still the best bet for a definitive diagnosis. Radiomics also offers several advantages and should be exploited to the maximum. The mechanisms of PCOS onset and progression are not very well known but pituitary dysfunction and elevated gonadotrophin releasing hormone resulting in high levels of luteinizing hormone are indicative of an activated hypothalamic-pituitary-ovarian axis in PCOS. A number of studies have also identified signaling pathways such as PI3K/Akt, NF-κB and STAT in PCOS etiology. The links of these signaling pathways to inflammation further underline the importance of inflammation in PCOS, which needs to be resolved for improving patient outcomes.

Mutations causing dysfunction of tubulins and microtubule-associated proteins, also known as tubulinopathies, are a group of recently described entities that lead to complex brain malformations. Anatomical and functional consequences of the disruption of tubulins include microcephaly, combined with abnormal corticogenesis due to impaired migration or lamination and abnormal growth cone dynamics of projecting and callosal axons. Key imaging features of tubulinopathies are characterized by three major patterns of malformations of cortical development (MCD): lissencephaly, microlissencephaly, and dysgyria. Additional distinctive MRI features include dysmorphism of the basal ganglia, midline commissural structure hypoplasia or agenesis, and cerebellar and brainstem hypoplasia. Tubulinopathies can be diagnosed as early as 21-24 gestational weeks using imaging and neuropathology, with possible extreme microlissencephaly with an extremely thin cortex, lissencephaly with either thick or thin/intermediate cortex, and dysgyria combined with cerebellar hypoplasia, pons hypoplasia and corpus callosum dysgenesis. More than 100 MCD-associated mutations have been reported in TUBA1A, TUBB2B, or TUBB3 genes, whereas fewer than ten are known in other genes such TUBB2A, TUBB or TUBG1. Although these mutations are scattered along the α- and β-tubulin sequences, recurrent mutations are consistently associated with almost identical cortical dysgenesis. Much of the evidence supports that these mutations alter the dynamic properties and functions of microtubules in several fashions. These include diminishing the abundance of functional tubulin heterodimers, altering GTP binding, altering longitudinal and lateral protofilament interactions, and impairing microtubule interactions with kinesin and/or dynein motors or with MAPs. In this review we discuss the recent advances in our understanding of the effects of mutations of tubulins and microtubule-associated proteins on human brain development and the pathogenesis of malformations of cortical development.

Centrioles are microtubule-based cell organelles present in most eukaryotes. They participate in the control of cell division as part of the centrosome, the major microtubule-organizing center of the cell, and are also essential for the formation of primary and motile cilia. During centriole assembly as well as across its lifetime, centriolar tubulin display marks defined by post-translational modifications (PTMs), such as glutamylation or acetylation. To date, the functions of these PTMs at centrioles are not well understood, although pioneering experiments suggest a role in the stability of this organelle. Here, we review the current knowledge regarding PTMs at centrioles with a particular focus on a possible link between these modifications and centriole's architecture, and propose possible hypothesis regarding centriolar tubulin PTMs's function.

Haploid gametes are produced from diploid parents through meiosis, a process inherent to all sexually reproducing eukaryotes. Faithful chromosome segregation in meiosis is essential for reproductive success, although it is less clear how the meiotic spindle achieves this compared to the mitotic spindle. It is becoming increasingly clear that tubulin post-translational modifications (PTMs) play critical roles in regulating microtubule functions in many biological processes, and meiosis is no exception. Here, I review recent advances in the understanding of tubulin PTMs in meiotic spindles, especially focusing on their roles in spindle integrity, oocyte aging, and non-Mendelian transmission.

Blood platelets are small non-nucleated cellular fragments that prevent and stop hemorrhages. They are produced in the bone marrow by megakaryocytes through megakaryopoiesis. This intricate process involves profound microtubule rearrangements culminating in the formation of a unique circular sub-membranous microtubule array, the marginal band, which supports the typical disc-shaped morphology of platelets. Mechanistically, these processes are thought to be controlled by a specific tubulin code. In this review, we summarize the current knowledge on the key isotypes, notably β1-, α4A- and α8-tubulin, and putative post-translational modifications, involved in platelet and marginal band formation. Additionally, we provide a provisional list of microtubule-associated proteins (MAPs) involved in these processes and a survey of tubulin variants identified in patients presenting defective platelet production. A comprehensive characterization of the platelet tubulin code and the identification of essential MAPs may be expected in the near future to shed new light on a very specialized microtubule assembly process with applications in platelet diseases and transfusion.

The organ of Corti, located in the cochlea within the inner ear is the receptor organ for hearing. It converts auditory signals into neuronal action potentials that are transmitted to the brain for further processing. The mature organ of Corti consists of a variety of highly differentiated sensory cells that fulfil unique tasks in the processing of auditory signals. The actin and microtubule cytoskeleton play essential function in hearing, however so far, more attention has been paid to the role of actin. Microtubules play important roles in maintaining cellular structure and intracellular transport in virtually all eukaryotic cells. Their functions are controlled by interactions with a large variety of microtubule-associated proteins (MAPs) and molecular motors. Current advances show that tubulin posttranslational modifications, as well as tubulin isotypes could play key roles in modulating microtubule properties and functions in cells. These mechanisms could have various effects on the stability and functions of microtubules in the highly specialised cells of the cochlea. Here, we review the current understanding of the role of microtubule-regulating mechanisms in the function of the cochlea and their implications for hearing, which highlights the importance of microtubules in the field of hearing research.

Microtubules are cytoskeletal elements that play key roles throughout the different steps of sperm development. As an integral part of the sperm flagellum, the molecular machine that generates sperm motility, microtubules are also essential for the progressive swimming of sperm to the oocyte, which is a prerequisite for fertilisation. Given the central role of microtubules in all steps of spermatogenesis, their functions need to be tightly controlled. Recent work has showcased tubulin posttranslational modifications as key players in sperm development and function, with aberrations often leading to male infertility with a broad spectrum of sperm defects. Posttranslational modifications are part of the tubulin code, a mechanism that can control microtubule functions by modulating the properties of their molecular building blocks, the tubulin proteins. Here we review the current knowledge on the implications of the tubulin code in sperm development and functions and its importance for male fertility.

Among the variety of post-translational modifications to which microtubules are subjected, the detyrosination/re-tyrosination cycle is specific to tubulin. It is conserved by evolution and characterized by the enzymatic removal and re-addition of a gene-encoded tyrosine residue at the C-terminus of α-tubulin. Detyrosinated tubulin can be further converted to Δ2-tubulin by the removal of an additional C-terminal glutamate residue. Detyrosinated and Δ2-tubulin are carried by stable microtubules whereas tyrosinated microtubules are present on dynamic polymers. The cycle regulates trafficking of many cargo transporting molecular motors and is linked to the microtubule dynamics via regulation of microtubule interactions with specific cellular effectors such as kinesin-13. Here, we give an historical overview of the general features discovered for the cycle. We highlight the recent progress toward structure and functioning of the enzymes that keep the levels of tyrosinated and detyrosinated tubulin in cells, the long-known tubulin tyrosine ligase and the recently discovered vasohibin-SVBP complexes. We further describe how the cycle controls microtubule functions in healthy neurons and cardiomyocytes and how deregulations of the cycle are involved in dysfunctions of these highly differentiated cells, leading to neurodegeneration and heart failure in humans.

Protists are an exceptionally diverse group of mostly single-celled eukaryotes. The organization of the microtubular cytoskeleton in protists from various evolutionary lineages has different levels of sophistication, from a network of microtubules (MTs) supporting intracellular trafficking as in Dictyostelium, to complex structures such as basal bodies and cilia/flagella enabling cell motility, and lineage-specific adaptations such as the ventral disc in Giardia. MTs building these diverse structures have specific properties partly due to the presence of tubulin post-translational modifications (PTMs). Among them there are highly evolutionarily conserved PTMs: acetylation, detyrosination, (poly)glutamylation and (poly)glycylation. In some protists also less common tubulin PTMs were identified, including phosphorylation, methylation, Δ2-, Δ5- of α-tubulin, polyubiquitination, sumoylation, or S-palmitoylation. Not surprisingly, several single-celled organisms become models to study tubulin PTMs, including their effect on MT properties and discovery of the modifying enzymes. Here, we briefly summarize the current knowledge on tubulin PTMs in unicellular eukaryotes and highlight key findings in protists as model organisms.

The importance of translation fidelity has been apparent since the discovery of genetic code. It is commonly believed that translation deviating from the main coding region is to be avoided at all times inside cells. However, ribosome profiling and mass spectrometry have revealed pervasive noncanonical translation. Both the scope and origin of translational "noise" are just beginning to be appreciated. Although largely overlooked, those translational "noises" are associated with a wide range of cellular functions, such as producing unannotated protein products. Furthermore, the dynamic nature of translational "noise" is responsive to stress conditions, highlighting the beneficial effect of translational "noise" in stress adaptation. Mechanistic investigation of translational "noise" will provide better insight into the mechanisms of translational regulation. Ultimately, they are not "noise" at all but represent a signature of cellular activities under pathophysiological conditions. Deciphering translational "noise" holds the therapeutic and diagnostic potential in a wide spectrum of human diseases.